Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.
- 1 November 1981
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 78 (11) , 6858-6862
- https://doi.org/10.1073/pnas.78.11.6858
Abstract
During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.This publication has 41 references indexed in Scilit:
- Relationship between fluorescent age pigment, physiological age and physical activity in the housefly, Musca domesticaMechanisms of Ageing and Development, 1981
- Plasma and urine uric acid levels: Heritability estimates and correlation with IQJournal of Human Genetics, 1980
- Cell differentation, aging and cancer: The possible roles of superoxide and superoxide dismutasesMedical Hypotheses, 1980
- Mutagenic activity of ascorbate in mammalian cell culturesCancer Letters, 1980
- Inhibition of nitrosamine formation by ascorbic acid: participation of free radicals in its anaerobic reaction with nitriteCellular and Molecular Life Sciences, 1980
- Isolation of an activator for prostaglandin hydroperoxidase from bovine vesicular gland cytosol and its identification as uric acidBiochemical and Biophysical Research Communications, 1979
- Interaction of DNA and liposomes as a model for membrane-mediated DNA damageNature, 1977
- Singlet oxygen formation during hemoprotein catalyzed lipid peroxide decompositionBiochemical and Biophysical Research Communications, 1977
- Serum uric acid levels in normal pregnancy with observations on the renal excretion of urate in pregnancyJournal of Clinical Pathology, 1966
- Kinetics of uric acid transport in human erythrocytesBiochimica et Biophysica Acta, 1961